Adaptive immunity 2 Flashcards
1
Q
Describe the basics of lymphocyte activation, differentiation, memory and effector responses
A
- antigen recognition - receptor has to recognise the antigen being presented to it by APC
- if there are other stimulatory signals - T cells are activated
- this causes secretion of IL-2R cytokine (main T cell growth factor)
- acts as an autocrine loop - drives clonal expansion of antigen specific cell
- also have differentiation of the responding cell - differentiate into a particular effector cell that actively performs its funtion
- differentiate into memory cells
2
Q
What is the 2 signal hypothesis for T cell activation?
A
- co-stimulatory signals required for optimal T cell activation and proliferation
- signal 1 - antigen-specific TCR engagament
- signal 2 - contact with co-stimulatory ligands
- signal 3 - cytokines directing T cell differentiation into distinct effectory cell types
3
Q
What are the positive co-stimulatory receptors that facilitate activation and proliferation? (signal 2)
A
- CD28
- 44kDa glycoprotein homodimer - expressed on majority of T cells
- binds to CD80 and CD86 expressed by APCs
- initial activation events
- ICOS
- inducible co-stimulator
- binds ICO-ligand on activated APCs
- expressed on memory cells and effector T cells
- help to maintain activity of already differentiated cells
4
Q
What are the negative co-stimulatory receptors (help turn activation off)
A
- CTLA-4
- induced within 24 hours after after activation, peaks 2-3 days post-stimulation
- binds to CD80/86 with higher affinity than CD28, but shuts down signaling pathways
- PD-1
- programme death 1 CD279 and BTLA
- PD-1 - help to mediate T cell tolerance in non-lympoid tissues
- BTLA - down regulate inflam and autoimmune responses
- programme death 1 CD279 and BTLA
5
Q
What is clonal anergy?
A
- state of non-responsiveness
6
Q
When does clonal anergy occur?
A
- if a co-stimulatory signal is absent
- helps to provide tolerance (especially in periphery)
- if only 1 signal is recieved - cell in rendered nonresponsive
- might happen if a T cell isnt screened against peripheral self-antigen during development
7
Q
In T cell activation, what do the initial signals 1 and 2 induce?
A
- up-regulation of pro-survival genes
- transcription of IL-2 and IL-2R genes
- IL-2 is an example of an autocrine type of cytokine response system
- outcome is activation and robust proliferation
- production of memory and effecrot clonal cell pops
8
Q
Describe what happens during signal 3
A
- depending on which cytokines are present as the T cell becomes activated, different outcomes can occur
- cytokines can send the T cell down different subset development pathways
9
Q
What are theb CD4 T cell distinct subsets?
A
- Th1 and Th2
- Th17
- Treg
- Tfh - (follicular)
10
Q
How do PAMPs aid in T cell differentiation?
A
- PAMPs bind to PRRs on the APC
- different PPRs = different cytokines produced
- viruses stimulate IL-12 to induce Th1 subsets
- worms stimulate IL-4 to induce Yh2 subsets
- this creates the cytokine evironment that drives the T cell down a pathway
- APC detect PAMP (virus, bacteria etc)
- produce a cytokine environment that drives the helper cell to become the most appropriare population to deal with infection
11
Q
A